Poly (oxyalkylene)-alpha, omega-dicarboxylic acids are finding ever increasing applications in various branches of chemistry. Some of the applications are as follows:
1. Water soluble support for Merrifield type peptide synthesis (R. P. Garfield and G. M. Ananthramaiah, J. Am. Chem. Soc. 101, 3394 (1979), G. P. Royer, Methods Enzymol. 136, 302 (1987)). PA0 2. Polymeric drug carriers--prodrugs (K. Ulbrich and J. Kopecek, Macromol. Chem. 187, 1131 (1986), T. Ouchi, Y. Hogihara, K. Takashashi, Y. Takano and I. Igarashi, Drug Design and Discovery, 9, 93 (1992), R. B. Greenwald, C. W. Gilbert, A. Pendri, C. D. Conover, J. Xia and A. Maertinez, J. Med. Chem. 39, 424 (1996), S. Zalipski, C. Gilon and A. Zilkha, Eur. Polym. J. 19, 1177 (1983), M. Pecher, J. Strochalm and K. Ulbrich, Makromol. Chem. Phys. 198, 1009 (1997)). PA0 3. Antistatic agents in polyamide/s (I. Jan and C. Frantisek, Czech. CS. 234,832). PA0 4. Conjugates with enzyme-metal ion for improved stability and activity of enzymes (Y. Tukayuki, M. Takeshi, T. Katsunobu, S. Yuji, T. Yukata and I. Yuji, Biochem. Biophys. Res. Commun. 145, 908 (1987), N. Veyarma, M. Nakata and A. Nakamura, Polym. J. (Tokkyo) 17, 721 (1985), T. Katsunobu, O. Kimiko, Y. Takayuki, S. Yuji, K. Yoh, M. Ayako and I. Yuji, J. Biotechnol 8, 135 (1988)). PA0 5. Conjugates with hemoglobin for oxygen carrying blood substitute (A. Yabuki, K. Yamaji, H. Ohki and Y. Iwashita, Transfusion (Philadelphia) 30,516 (1990). PA0 6. Conjugates with lipids for improved longevity in blood circulation (3. Gabriel and C. Greger, Biochem. Biophys. Acta. 1146, 157 (1993). PA0 7. Surface modyfying agents for transition metal alluminides (D. M. Zehner, Surf. Rev. Lett. 3, 1637 (1996). PA0 8. Stabilizer for water based epoxy formulations (H. E. Friend and C. J. Stark, PCT Intl. Appl. WO 9619, 514) and so on.
In order to meet these growing requirements for poly (oxyalkylene)-alpha, omega-dicarboxylic acids, various methods for their preparation have been developed so far which can broadly be classified into following two types.
1. Carboxymethylation of poly (oxyalkylene glycol)s.
In this method of preparation, terminal hydroxymethyl groups of poly (oxyalkylene glycol)s are derivatized with carboxymethyl groups (--CH.sub.2 --COOH groups) so as to obtain poly (oxyalkylene)-alpha, omega-dicarboxylic acids. This method essentially involves following steps: A) Activation of terminal hydroxyl groups by reacting poly (oxyalkylene glycol)s with strong bases such as potassium tertiary butoxide, silver oxide, sodium hydroxide etc. B) Reaction of alcoholate so obtained with reagents like bromo ethyl acetate, chloroethyl acetate etc. C) Saponification of ethyl ester followed by acidification of reaction mixture. D) Isolation of product.